BACKGROUND To describe the precise location of transition zone (TZ) and anterior fibromuscular stroma (AFMS) prostate cancers (TZ/AFMS) within histological zones at various stages of development and to demonstrate their pattern of intraprostatic spread from their site of origin. METHODS Anterior TZ/AFMS cancers excluding the anterolateral part of peripheral zone, were identified from radical prostatectomy specimens. Morphometric histopathological study included largest surface area, volume and spatial distribution. RESULTS Out of 91 TZ/AFMS cancers, 79 were <4 cm3 and 69 <2 cm3. Fifty percent and 70% of cancers <4 cm3 were located in the anterior third and inferior half of TZ and/or AFMS, respectively. Cancers <2 cm3 could be classified into three types according to their location related to histologic zone boundaries: TZ type 1 (40%) for cancers confined to one TZ lobe; TZ type 2 (35%) for cancers most represented in one TZ lobe but crossing its anterior boundary; type AFMS (25%) for cancers confined to AFMS. These results form the rationale for the hypothesis that AFMS cancers originate from anterior and medial TZ and due to benign prostatic hypertrophy they become excluded from TZ, anteriorly into AFMS. TZ anterior limit would then act as a barrier to their posterior extension. CONCLUSIONS TZ/AFMS cancers contours and locations are predictable and conform to histological zones boundaries. Knowledge of these cancer origin and pattern of spread in TZ and AFMS are of importance for imaging diagnosis, guidance for biopsy and focal therapy. Prostate 69: 105–113, 2009. © 2008 Wiley–Liss, Inc.